[Synthesis]
General procedure for the synthesis of 1-fluoro-3-methoxy-5-methylbenzene from trimethylcyclotriboroxane and 3-bromo-5-fluoroanisole (Example 40):
(40a) Synthesis of 1-fluoro-3-methoxy-5-methylbenzene
3-Bromo-5-fluoroanisole (2.05 g, 10 mmol), trimethylcyclotriboroxane (50% THF solution, 2.51 g, 20 mmol), PdCl2(dppf) (0.82 g, 1.0 mmol), and cesium carbonate (6.52 g, 20 mmol) were dissolved in a solvent mixture of dioxane (100 mL) and water (50 mL). It was heated and stirred under reflux conditions for 10 hours. Upon completion of the reaction, it was cooled to room temperature and water (100 mL) was added to the reaction solution, which was then extracted twice with ethyl acetate (200 mL). The organic layers were combined, washed twice with water (100 mL) and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate, 6:1) to afford 1-fluoro-3-methoxy-5-methylbenzene (1.40 g, yield: 66%) as a yellow oil.
1H-NMR (CDCl3, 400 MHz) δ: 1.78 (3H, s), 6.44 (1H, dd, J = 2.0, 11.0 Hz), 6.50 (1H, d, J = 11.0 Hz), 6.51 (1H, s). |